Question:
Was the Holy Prophet poisoned (or killed) and martyred or did he die a natural death?
Answer:
In general, the famous opinion (among the Shi’a and Sunni scholars) is that the Prophet (P) was poisoned by a Jewish woman after the battle of Khaibar. We do have a narration with a sound chain of narrators which states this.
However, there is a problem with the content of the narration. In the narration, the Jewish woman says that if Muhammad (pbuh) were to eat from the food, this would prove he is not a prophet! Therefore, if we believe the Prophet ate from this food and was poisoned by it, we are doubting his prophecy. In addition, the Holy Qur’an states “and We protect you from the people”, thus indicating the Prophet was safe from such plots.
Other evidence for the Prophet being martyred comes from the narration of Imam Sadiq (a.s): “There is none of us but is killed by sword or poison.”
The problems with this narration:
    It is mursal (i.e. does not have a continuous chain of narrators)
    It is most likely talking about the twelve Imams (as). This is proven by another hadith from Imam al-Hasan (as) talking about the Imams in particular, in which he says: “There is none of us (Imams) except he is poisoned or killed” (Biharul Anwar, 27:216)
Finally, there is a narration in Tafsir al-Ayyashi which states that the Prophet (pbuh) was poisoned by his two wives, A’isha and Hafsa.
The problems with this narration
    It is only one narration
    It is mursal (does not have a continuous chain of narrators) and is therefore weak
    It is definitely not the opinion of our mainstream scholars
    Absolute majority of our jurists (based on many authentic narrations) observe that the meat of the People of the Book is not Halal. However, Kosher is considered Halal by Sunnis. How then could the Prophet accept a meat cooked (and the goat would be normally killed by people at home) by a Jewess?!
    We can’t rule according to this narration because without any prejudice according to the Sharia’ law one would be found guilty for murdering if:
    a) Two just male witnesses give their testimony for it (just because a story is famous even among our respected scholars doesn’t mean its true. It is proven in the Principle of jurisprudence that الشهره is not a religious evidence. ربّ مشهور لا اصل له)
    b) The murderer confesses that he/she has killed the murdered one.
None of the above conditions are met with regards to the two wives
 Yes, it is narrated in al-Bukhari and Muslim from Ayesha that they gave a medicine to the Prophet prior to his death:
 “’Aisha said: we gave him (pbuh) medicine while he was ill. He (pbuh) kept signalling to us not to give him the medicine. We thought it to be the dislike of an ill person for taking medicine. When he woke up he (pbuh) said: ‘did I not prohibit you from giving me medicine?’ We said: ‘we thought it was the dislike of the patient for medicine’. He said: ‘everyone in the house should take from the medicine while I watch them, except for Abbas (the Prophet’s uncle) because he was not present (when the medicine was being given to the Prophet pbuh)”.

The problems with this narration:
    The narration does not say it was poison (thus no confession).
    The narration is not mentioned in our books of hadith
    The content of the hadith is problematic. Why would the Prophet punish all in the household except Abbas by making them drink the medicine? And if it was poison, they should all have died too
Other problems with the theory that the Prophet was poisoned:
If someone is poisoned he is usually expected to die soon after such as the case of Imam Hasan (a.s) not after about four years.
Also, the Almighty God says the following about the plots of hypocrites in assassinating the Prophet, which indicates although there have been attempt in killing the Prophet they did not succeed.

“and they resolved that (plot to murder Prophet Muhammad SAW) which they were unable to carry out” (9:74)
In conclusion, it seems most likely that the Prophet (pbuh) died of natural causes and was not poisoned. And God knows best.
Answered by: Sheikh Mansour Leghaei